Reslizumab for Poorly Controlled, Eosinophilic Asthma A Randomized, Placebo-controlled Study

Washington University School of Medicine, St. Louis, MO 63110, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 08/2011; 184(10):1125-32. DOI: 10.1164/rccm.201103-0396OC
Source: PubMed

ABSTRACT Eosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of eosinophils.
To evaluate the effect of the antibody to IL-5, reslizumab, in patients with eosinophilic asthma that is poorly controlled with high-dose inhaled corticosteroid.
Patients were randomly assigned to receive infusions of reslizumab at 3.0 mg/kg (n = 53) or placebo (n = 53) at baseline and at Weeks 4, 8, and 12, with stratification by baseline Asthma Control Questionnaire (ACQ) score less than or equal to 2 or greater than 2. The primary efficacy measure was the difference between the reslizumab and placebo groups in the change in ACQ score from baseline to end of therapy (Week 15 or early withdrawal).
Mean changes from baseline to end of therapy in ACQ score were -0.7 in the reslizumab group and -0.3 in the placebo group (P = 0.054) and in FEV(1) were 0.18 and -0.08 L, respectively (P = 0.002). In those patients with nasal polyps, the changes in ACQ score were -1.0 and -0.1, respectively (P = 0.012). Median percentage reductions from baseline in sputum eosinophils were 95.4 and 38.7%, respectively (P = 0.007). Eight percent of patients in the reslizumab group and 19% of patients in the placebo group had an asthma exacerbation (P = 0.083). The most common adverse events with reslizumab were nasopharyngitis, fatigue, and pharyngolaryngeal pain.
Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.


Available from: Mario Castro, May 08, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biologic agents (also termed biologicals or biologics) are therapeutics that are synthesized by living organisms and directed against a specific determinant, for example a cytokine or receptor. In inflammatory and autoimmune diseases, biologicals have revolutionized the treatment of several immune-mediated disorders. Biologicals have also been tested in allergic disorders. These include agents targeting IgE; T helper 2 (Th2)-type and Th2-promoting cytokines, including interleukin-4 (IL-4), IL-5, IL-9, IL-13, IL-31 and thymic stromal lymphopoietin (TSLP); pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17A, IL-17F, IL-23 and tumor necrosis factor-α (TNF); chemokine receptor CCR4; and lymphocyte surface and adhesion molecules, including CD2, CD11a, CD20, CD25, CD52 and OX40 ligand. In this task force paper of the Interest Group on Biologicals of the European Academy of Allergy and Clinical Immunology we review biologicals that are currently available or tested for the use in various allergic and urticarial pathologies, by providing an overview on their state of development, area of use, adverse events, and future research directions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Allergy 03/2015; DOI:10.1111/all.12616 · 6.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glucocorticoids are commonly used for treating asthma and its exacerbations but have well-recognised adverse effects and are not always effective. Few alternative treatments exist. Using a murine model of an acute exacerbation of asthma, we assessed the ability of ISU201, a novel protein drug, to suppress the inflammatory response when administered after induction of an exacerbation. Sensitised mice were chronically challenged with a low mass concentration of aerosolised ovalbumin, and then received a single moderate-level challenge to simulate an allergen-induced exacerbation. ISU201 was administered to mice 2 and 8 hours later, while pulmonary inflammation and expression of mRNA for chemokines and proinflammatory cytokines were assessed after 4, 12, and 24 hours. Relative to vehicle-treated controls, ISU201 suppressed accumulation of pulmonary neutrophils and eosinophils, while accelerating the decline in CXCL1, TNF-α, and IL-6 in lavage fluid and lung tissue. ISU201 significantly reduced peak expression of mRNA for the chemokines Cxcl9 and Cxcl10, the adhesion molecules Icam1 and Vcam1, and the proinflammatory cytokines Il1b, Il12p40, and Csf1. The ability of ISU201 to promote resolution of inflammation suggests that it may have potential as an alternative to glucocorticoids in the management of asthma, including when administered after the onset of an acute exacerbation.
    Mediators of Inflammation 02/2015; 2015:405629. DOI:10.1155/2015/405629 · 2.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies correlate vitamin D deficiency with asthma severity. Calcitriol modulates receptor and cytokine expression from various leukocytes in an anti-inflammatory manner. Despite eosinophil activity during mucosal inflammation, knowledge on the direct effect of calcitriol on this granulocyte is very limited. We propose that calcitriol exerts direct effects on eosinophil biology by modulating its programmed cell death pathways and other functions. Purified peripheral blood eosinophils from atopic donors were incubated with calcitriol (10nM) for up to 14 days with and without IL-5. We observed that calcitriol significantly reduced eosinophil necrosis and cytolytic release of EPX in media when co-incubated with IL-5. The addition of calcitriol also significantly decreased CRTh2 and CCR10 expression on eosinophils. Eosinophil cytotoxic mediator release into mucosal tissues, resulting from necrotic cytolysis, as well as eosinophil recruitment to lungs are major contributors to airway inflammation in allergic asthma. Hence, the reduction of mucosal inflammation achieved by decreasing eosinophil necrosis and recruitment unveil new anti-inflammatory mechanisms for calcitriol in the context of airway inflammation.
    08/2014, Degree: Master of Science in Experimental Medicine, Supervisor: Francis Davoine